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572 The contractile activities of lipoxin A4 and lipoxin B4 on guinea pig airways
571
ANTI-ALLERGIC ACTIVITY OF AN ORAL BETA2 AGONIST, CLENBUTEROL. J .Fabre, J. BousB. Lebel, J.L.Jirou-Najou, M.Cluzel, P. quet, Godard, F.B.Michel, France. Beta-2-agonists block mediator release from mast cells but their role in the treatment of allergic rhinitis remains unclear. Clenbuterol (Cl, an oral beta-2-agonist was tested in a double-blind placebo-controlled study in 7 grass pollen allergic patients. Anti-allergic activity was tested by nasal challenge with 3-fold increasing numbers of orchard grass pollens (SO-12,250 grains). Positivity was assessed by symptom scores and release of histamine (RIA, Immunotech) and PCD2 (EIA) in nasal secretions. Skin prick tests with six 3-fold increasing concentrations of a standardized orchard grass pollen extract were analysed by parallel line bioassay. Histamine release from whole blood with eight lo-fold concentrations was also done. Patients were tested 3 times at 2 wk interval, at baseline, and after 15 days of placebo (P) or clenbuterol (8Opg BID). C increased significantly (p=O.O3, Wilcoxon) the number of grains eliciting a positive challenge (C:l,OSO grains, P: 307, control: 278). Histamine release in nasal secretions was blocked in 6/7 subjects by C. PGD2 release was unmodified by C. Dose-response curves of skin tests were parallel on the 3 test days but were significantly (p=O.Ol, Wilcoxon) decreased by C. C had no effect on histamine release from blood basophils. C has anti-allergic properties but its effect is too small for being clinically relevant.
572
THE CONTRACTILR ACTIVITIES OF LIPGXIN A4 AND LIPGXIN B4 ON GUINRA PIG AIRWAYS. C Jacques, A Crea, B Spur, T Ii Lee. London U.K. Lipoxins are a novel group of recently characterised oxygenation products derived from arachidonic acid. The isometric contractile activities of lipoxin A4 (LxA4) and lipoxin B4 (LxB4) have been assessed on guinea pig parenchymal strips and tracheal spirals over the dose range 1OnM to 1OuM. LxA4 contracted parenchymal strips; the concentration eliciting 50% maximum histamine response was 3 x IO-‘M. LxA4 did not affect tracheal spirals. The LxA4 dose-response curve was parallel to that of leukotriene D4 (LTD4) with LxA4 being approximately lO,OOO-fold less potent than LTD4. LxA4 has a time course for eliciting contraction which is similar to that for LTD4: the response was slow in onset and did not plateau for up to 20 minutes. The LxA4 dose-response curve for parenchymal strips was displaced to the right in the presence of increasing doses of the LTD4 Preanatagonists, FPL 55712 or L-64:223. in ubation of tissues with 1 x 10 M and 1 x 10-f M L-651392, a 5-lipoxygenase inhibitor, or 1OuM indomethacin, a cycle-oxygenase inhibitor, did not affect the contractile activity of LxA4. LxB4 did not constrict parenchymal strips or tracheal spirals.
573
DEXTROUETORPH~N (DUPl INDUCES EARLY PHPSE (EPl SKIN BUT NOT BRONCHIRL REIICTIDNS fle444~~4 E4e4tur !h BQQ~C !!4m444~ !!I, LYQ~QQ Institute for hrdicrl L !!4Q4fir,l9L !a ’ El PIIO Rssarrch rnd Davaloprrnt, El Paso, TX 79902. DilP is 1 nonnrrcotic contrrlly actin rntitusoivo choricrlly ralrtrd to codeine. Liks codeine it is caprbla of inducin9 systcric and cutrnlous histrains rrlrrrr Via a nonirrunolopic~l phrraocologicrl rction. Recent studies show lunp rant crlls differ free skin mart collr in hirtolopy, hirtocharirtry, tryptrro content and histrrinr rolrrsin9 rachrnirrs. To assass rhcthrr or not DUP rctivrtrs lunp l ast CIllS, WI prrformd sirultrnrous skin rnd bronchial challonpor in 5 rtopic rsthortic subjocta. DIP skin and bronchial chrllonpor uoro procodmd and follourd within 49 hours by histrrinr bronchial chrllonprr. All rubjoctr deronntrrtod positive EP skin rooctionr to DllP (l.Sxhistrrino control) at the lowrst concrntrrtion used in the bronchirl chrllrn9o ~O.OlDo91all. No lrtr phrso skin reactions occurrod. &ll rubjoctr hod positive histraino bronchial EP rorctions the dry brforo and the dry rftor DIP chrllongo. FInon PC20 histrrinr brforo DtiP did not differ fror histrrinr poxt DNP chrllonpo. rm-t PC20 Inhrlation chrllen9os with DHP up to S brorthr of so l 9/al resultrd in noithor EP nor lrto bronchial roactionr in any of thr subjoctr. Wt concludr thrt DtlP does not rctivrtr lun9 rrrt ~011s IS l vidoncod by frilurr of DltP to induce bronchosprrr in hixtrrinr-ronsitivo rsthartic subjects.
Colchicine CC.> corrected the low Con-A Suprressor T-cell function of patients with Allergic Asthma (A.As.),(D. Ilfeld et al. Clin. Exp. Immunol 61. 360: 1965). In this studv we evaluated the in-viva-effect-of C. on patients with A.As. 11 patients with known A.As., who were treated with daily long acting Theophylline drugs, received C. l/2 gr, twice daily, given in a double blind cross over fashion. Each treatment period lasted 4 weeks. During each period, patients were followed by daily clinical score and peak expiratory flow rates, skin wheal response and bronchial inhalation challenge with allergen, end Con-A suppressor T-cell function as described in the literature. The meen clinical score for the entire group as well as the No. of salbutamol inhalation used while on C. treatment significantly inproved when conparad to the placebo period (P
challenge
and
the
skin
response
to
the allergens C. significantly corrected the low supressor T-cell function (P
311
ANTI-ALLERGIC ACTIVITY OF AN ORAL BETA2 AGONIST, CLENBUTEROL. J .Fabre, J. BousB. Lebel, J.L.Jirou-Najou, M.Cluzel, P. quet, Godard, F.B.Michel, France. Beta-2-agonists block mediator release from mast cells but their role in the treatment of allergic rhinitis remains unclear. Clenbuterol (Cl, an oral beta-2-agonist was tested in a double-blind placebo-controlled study in 7 grass pollen allergic patients. Anti-allergic activity was tested by nasal challenge with 3-fold increasing numbers of orchard grass pollens (SO-12,250 grains). Positivity was assessed by symptom scores and release of histamine (RIA, Immunotech) and PCD2 (EIA) in nasal secretions. Skin prick tests with six 3-fold increasing concentrations of a standardized orchard grass pollen extract were analysed by parallel line bioassay. Histamine release from whole blood with eight lo-fold concentrations was also done. Patients were tested 3 times at 2 wk interval, at baseline, and after 15 days of placebo (P) or clenbuterol (8Opg BID). C increased significantly (p=O.O3, Wilcoxon) the number of grains eliciting a positive challenge (C:l,OSO grains, P: 307, control: 278). Histamine release in nasal secretions was blocked in 6/7 subjects by C. PGD2 release was unmodified by C. Dose-response curves of skin tests were parallel on the 3 test days but were significantly (p=O.Ol, Wilcoxon) decreased by C. C had no effect on histamine release from blood basophils. C has anti-allergic properties but its effect is too small for being clinically relevant.
572
THE CONTRACTILR ACTIVITIES OF LIPGXIN A4 AND LIPGXIN B4 ON GUINRA PIG AIRWAYS. C Jacques, A Crea, B Spur, T Ii Lee. London U.K. Lipoxins are a novel group of recently characterised oxygenation products derived from arachidonic acid. The isometric contractile activities of lipoxin A4 (LxA4) and lipoxin B4 (LxB4) have been assessed on guinea pig parenchymal strips and tracheal spirals over the dose range 1OnM to 1OuM. LxA4 contracted parenchymal strips; the concentration eliciting 50% maximum histamine response was 3 x IO-‘M. LxA4 did not affect tracheal spirals. The LxA4 dose-response curve was parallel to that of leukotriene D4 (LTD4) with LxA4 being approximately lO,OOO-fold less potent than LTD4. LxA4 has a time course for eliciting contraction which is similar to that for LTD4: the response was slow in onset and did not plateau for up to 20 minutes. The LxA4 dose-response curve for parenchymal strips was displaced to the right in the presence of increasing doses of the LTD4 Preanatagonists, FPL 55712 or L-64:223. in ubation of tissues with 1 x 10 M and 1 x 10-f M L-651392, a 5-lipoxygenase inhibitor, or 1OuM indomethacin, a cycle-oxygenase inhibitor, did not affect the contractile activity of LxA4. LxB4 did not constrict parenchymal strips or tracheal spirals.
573
DEXTROUETORPH~N (DUPl INDUCES EARLY PHPSE (EPl SKIN BUT NOT BRONCHIRL REIICTIDNS fle444~~4 E4e4tur !h BQQ~C !!4m444~ !!I, LYQ~QQ Institute for hrdicrl L !!4Q4fir,l9L !a ’ El PIIO Rssarrch rnd Davaloprrnt, El Paso, TX 79902. DilP is 1 nonnrrcotic contrrlly actin rntitusoivo choricrlly ralrtrd to codeine. Liks codeine it is caprbla of inducin9 systcric and cutrnlous histrains rrlrrrr Via a nonirrunolopic~l phrraocologicrl rction. Recent studies show lunp rant crlls differ free skin mart collr in hirtolopy, hirtocharirtry, tryptrro content and histrrinr rolrrsin9 rachrnirrs. To assass rhcthrr or not DUP rctivrtrs lunp l ast CIllS, WI prrformd sirultrnrous skin rnd bronchial challonpor in 5 rtopic rsthortic subjocta. DIP skin and bronchial chrllonpor uoro procodmd and follourd within 49 hours by histrrinr bronchial chrllonprr. All rubjoctr deronntrrtod positive EP skin rooctionr to DllP (l.Sxhistrrino control) at the lowrst concrntrrtion used in the bronchirl chrllrn9o ~O.OlDo91all. No lrtr phrso skin reactions occurrod. &ll rubjoctr hod positive histraino bronchial EP rorctions the dry brforo and the dry rftor DIP chrllongo. FInon PC20 histrrinr brforo DtiP did not differ fror histrrinr poxt DNP chrllonpo. rm-t PC20 Inhrlation chrllen9os with DHP up to S brorthr of so l 9/al resultrd in noithor EP nor lrto bronchial roactionr in any of thr subjoctr. Wt concludr thrt DtlP does not rctivrtr lun9 rrrt ~011s IS l vidoncod by frilurr of DltP to induce bronchosprrr in hixtrrinr-ronsitivo rsthartic subjects.
Colchicine CC.> corrected the low Con-A Suprressor T-cell function of patients with Allergic Asthma (A.As.),(D. Ilfeld et al. Clin. Exp. Immunol 61. 360: 1965). In this studv we evaluated the in-viva-effect-of C. on patients with A.As. 11 patients with known A.As., who were treated with daily long acting Theophylline drugs, received C. l/2 gr, twice daily, given in a double blind cross over fashion. Each treatment period lasted 4 weeks. During each period, patients were followed by daily clinical score and peak expiratory flow rates, skin wheal response and bronchial inhalation challenge with allergen, end Con-A suppressor T-cell function as described in the literature. The meen clinical score for the entire group as well as the No. of salbutamol inhalation used while on C. treatment significantly inproved when conparad to the placebo period (P
challenge
and
the
skin
response
to
the allergens C. significantly corrected the low supressor T-cell function (P
311